Neuroprotective effect of preoperatively induced mild hypothermia as determined by biomarkers and histopathological estimation in a rat subdural hematoma decompression model ; Laboratory investigation

Shoji Yokobori, Shyam Gajavelli, Stefania Mondello, Jixiang Mo-Seaney, Helen M. Bramlett, W. Dalton Dietrich, M. Ross Bullock

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Object. In patients who have sustained a traumatic brain injury (TBI), hypothermia therapy has not shown efficacy in multicenter clinical trials. Armed with the post hoc data from the latest clinical trial (National Acute Brain Injury Study: Hypothermia II), the authors hypothesized that hypothermia may be beneficial in an acute subdural hematoma (SDH) rat model by blunting the effects of ischemia/reperfusion injury. The major aim of this study was to test the efficacy of temperature management in reducing brain damage after acute SDH. Methods. The rats were induced with acute SDH and placed into 1 of 4 groups: 1) normothermia group (37 C); 2) early hypothermia group, head and body temperature reduced to 33 C 30 minutes prior to craniotomy; 3) late hypothermia group, temperature lowered to 33 C 30 minutes after decompression; and 4) sham group, no acute SDH (only craniotomy with normothermia). To assess for neuronal and glial cell damage, the authors analyzed microdialysate concentrations of GFAP and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) by using a 100-kD probe. Fluoro-Jade B-positive neurons and injury volume with 2,3,5-triphenyltetrazolium chloride staining were also measured. Results. In the early phase of reperfusion (30 minutes, 2.5 hours after decompression), extracellular UCH-L1 in the early hypothermia group was significantly lower than in the normothermia group (early, 4.9 1.0 ng/dl; late, 35.2 12.1 ng/dl; normothermia, 50.20 28.3 ng/dl; sham, 3.1 1.3 ng/dl; early vs normothermia, p < 0.01; sham vs normothermia, p < 0.01, analyzed using ANOVA followed by a post hoc Bonferroni test). In the late phase of reperfusion (> 2.5 hours after decompression), extracellular GFAP in the early hypothermia group was also lower than in the normothermia and late hypothermia groups (early, 5.5 2.9 ng/dl; late, 7.4 3.4 ng/dl; normothermia, 15.3 8.4 ng/ dl; sham, 3.3 1.0 ng/dl; normothermia vs sham; p < 0.01). The number of Fluoro-Jade B-positive cells in the early hypothermia group was significantly smaller than that in the normothermia group (normothermia vs early: 774,588 162,173 vs 180,903 42,212, p < 0.05). Also, the injury area and volume were smaller in the early hypothermia group in which hypothermia was induced before craniotomy and cerebral reperfusion (early, 115.2 15.4 mm3; late, 344.7 29.1 mm3; normothermia, 311.2 79.2 mm3; p < 0.05). Conclusions. The data suggest that early, preoperatively induced hypothermia could mediate the reduction of neuronal and glial damage in the reperfusion phase of ischemia/reperfusion brain injury.

Original languageEnglish (US)
Pages (from-to)370-380
Number of pages11
JournalJournal of neurosurgery
Volume118
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Biomarker
  • Hypothermia
  • Ischemia/reperfusion injury
  • Microdialysis
  • Neuronal degeneration
  • Rat
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

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